Density functional theory study on the formation mechanism and electrical properties of two-dimensional electron gas in biaxial-strained LaGaO 3 /BaSnO 3 heterostructure.

The two-dimensional electron gas (2DEG) in BaSnO 3 -based heterostructure (HS) has received tremendous attention in the electronic applications because of its excellent electron migration characteristic. We modeled the n-type (LaO) + /(SnO 2 ) 0 interface by depositing LaGaO 3 film on the BaSnO 3 substrate and explored strain effects on the critical thickness for forming 2DEG and electrical properties of LaGaO 3 /BaSnO 3 HS system using first-principles electronic structure calculations. The results indicate that to form 2DEG in the unstrained LaGaO 3 /BaSnO 3 HS system, a minimum thickness of approximately 4 unit cells of LaGaO 3 film is necessary. An increased film thickness of LaGaO 3 is required to form the 2DEG for -3%-biaxially-strained HS system and the critical thickness is 3 unit cells for 3%-baxially-strained HS system, which is caused by the strain-induced change of the electrostatic potential in LaGaO 3 film. In addition, the biaxial strain plays an important role in tailoring the electrical properties of 2DEG in LaGaO 3 /BaSnO 3 HS syestem. The interfacial charge carrier density, electron mobility and electrical conductivity can be optimized when a moderate tensile strain is applied on the BaSnO 3 substrate in the ab-plane.

The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, it has a poor prognosis due to its highly invasive and metastatic nature. Consequently, identifying effective prognostic markers and potential therapeutic targets has been extensively investigated. METTL5, an 18S rRNA methyltransferase, is abnormally high in HCC. But its biological function and prognostic significance in HCC remain largely unelucidated. This study aimed to investigate the role of METTL5 in HCC progression, and elucidate its possible molecular mechanisms in HCC via transcriptome sequencing, providing new insights for identifying new HCC prognostic markers and therapeutic targets. METHODS: The METTL5 expression in HCC and paracancerous tissues was analyzed using HCC immunohistochemical microarrays and bioinformatic retrieval methods to correlate METTL5 with clinicopathological features and survival prognosis. We constructed a METTL5 knockdown hepatocellular carcinoma cell line model and an animal model to determine the effect of METTL5 on hepatocellular carcinoma progression. Subsequently, RNA sequencing was performed to analyze the molecular mechanism of METTL5 in HCC based on the sequencing results, and relevant experiments were performed to verify it. RESULTS: We found that METTL5 expression was elevated in hepatocellular carcinoma tissues and correlated with poor patient prognosis, and in the analysis of clinicopathological features showed a correlation with TNM staging. In hepatocellular carcinoma cell lines with knockdown of METTL5, the malignant biological behavior was significantly reduced both in vitro and in vivo. Based on the sequencing results as well as the results of GO functional enrichment analysis and KEGG pathway enrichment analysis, we found that METTL5 could promote the generation and release of neutrophil extracellular capture network (NETs) and might further accelerate the progression of HCC. CONCLUSION: The m6A methyltransferase METTL5 is overexpressed in hepatocellular carcinoma (HCC) and correlates with poor prognosis. METTL5 accelerates malignant progression of HCC by promoting generation and release of the neutrophil extracellular traps (NETs) network, providing new insights for clinical biomarkers and immunotherapeutic targets in HCC prognosis.

Physiological and biochemical characteristics of high and low Cd accumulating Brassica napus genotypes.

Phytoremediation is a widely used and cost-effective technique for in situ remediation of heavy metals. Brassica napus L. genotype with high Cd accumulation and strong Cd tolerance is an ideal candidate for phytoremediation. In this study, a hydroponic experiment was conducted to select a Brassica napus genotype with either high or low Cd accumulation from a panel of 55 genotypes. The physiological mechanisms governing Cd accumulation and Cd tolerance were then explored. BN400 and BN147 were identified as the high and low Cd accumulating genotypes, respectively. Additionally, BN400 exhibited greater tolerance to Cd stress compared to BN147. Root morphology analysis revealed that BN400 exhibited longer root length, smaller root surface area and root volume, and less root tips but bigger root diameter than BN147. Subcellular Cd distribution showed that the Cd concentrations in the cell wall and vacuole in shoot were significantly higher in BN400 than in BN147, whereas the opposite trend was observed in the roots.. Pectate/protein-integrated Cd was found to be the predominant form of Cd in both shoots and roots, with significantly higher levels in BN400 compared to BN147 in the shoot, but the opposite trend was observed in the roots. These results suggest that the long fine roots play a role in Cd accumulation. The high Cd accumulating genotype was able to retain Cd in leaf cell walls and vacuoles, and Cd was mainly present in the form of pectate/protein-integrated Cd, which contributes to its strong Cd tolerance. These findings have important implications for the screening and breeding of Brassica napus genotypes with high Cd accumulation for phytoremediation purposes.

Percutaneous Curved Vertebroplasty Versus Unilateral Percutaneous Vertebroplasty for Osteoporotic Vertebral Compression Fractures: A Systematic Review and Meta-Analysis.

BACKGROUND: Percutaneous curved vertebroplasty (PCVP), a modified traditional unilateral percutaneous vertebroplasty (UPVP) technique, is increasingly being used to treat osteoporotic vertebral compression fractures (OVCFs); however, its advantages remain controversial. This meta-analysis was conducted to determine whether PCVP is superior to traditional UPVP in treating OVCFs. METHODS: Six databases were searched for studies comparing the clinical efficacy of PCVP and UPVP in treating patients with OVCFs published until March 2023. After study selection, data extraction, and risk of bias evaluation, a meta-analysis was conducted. The study protocol was registered in the PROSPERO platform (registration number: CRD42023417190). RESULTS: Eight studies (6 randomized controlled trials and 2 cohort studies) were eligible for the final analysis. The pooled results revealed no between-group differences in operation time (P = 0.85), intraoperative fluoroscopy (P = 0.58), or postoperative short-term visual analog scale scores (P = 0.15). However, PCVP was associated with more injected cement (P = 0.003), a lower cement leakage rate (P = 0.006), and a lower final follow-up visual analog scale score (P < 0.0001). CONCLUSIONS: PCVP was superior to UPVP in terms of reducing the bone cement leakage rate and providing long-term pain relief. Further trials with larger sample sizes and longer follow-up periods are required to verify these findings owing to the potential risk of bias.

Mechanical properties of CTCs in patients with diagnosed ovarian cancer.

The incidence and mortality of gynecologic cancers have been constantly increasing in China over the last 2 decades, which become a major health concern for women. Survival rates of gynecologic cancers are generally not satisfactory and decrease along with the advancing stage, this is mainly due to the lack of a clear prognostic evaluation during the treatment, which brings difficulties to the treatment. Therefore, more accurate prognostic evaluation methods are urgently needed. To solve this problem, this article explores the changes in the biomechanical properties of cells. Changes in the biomechanical properties of circulating tumor cells (CTCs) were explored by nano detection technology. The reference criteria for clinical evaluation of ovarian cancer (Age, FIGO stage, Histologic type, CA-125, Ascites, Single/Double, Residual lesion, and Chemotherapy) were compared and analyzed. The results showed that the average cell height of CTCs was 4.12 ± 0.83 µm before chemotherapy and 4.87 ± 0.71 µm after chemotherapy, with an average increase of 18.203 %. The apparent Young's modulus (E) was 3.884 ± 0.045 kPa before chemotherapy and 4.514 ± 0.025 kPa after chemotherapy, which increased by 0.63 kPa. The ROC analysis of FIGO stage of ovarian cancer patients showed that Young's modulus of cells could better reflect the accuracy of the evaluation of FIGO stage of patients, with the accuracy reaching 76.7 %, which was higher than the detection accuracy of CA-125 (72.6 %). In conclusion, the mechanical properties of CTCs can indicate the FIGO stage and diagnosis of patients and predict the prognostic risk of patients.

The activated CD36-Src axis promotes lung adenocarcinoma cell proliferation and actin remodeling-involved metastasis in high-fat environment.

Obesity/overweight and lipid metabolism disorders have become increased risk factors for lung cancer. Fatty acid translocase CD36 promotes cellular uptake of fatty acids. Whether and how CD36 facilitates lung adenocarcinoma (LUAD) growth in high-fat environment is unknown. Here, we demonstrated that palmitic acid (PA) or high-fat diet (HFD) promoted LUAD cell proliferation and metastasis in a CD36-dependent manner. Mechanistically, CD36 translocated from cytoplasm to cell membrane and interacted with Src kinase upon PA stimulation in human LUAD cells. Akt and ERK, downstream of Src, were then activated to mediate LUAD cell proliferation and metastasis. Furthermore, PA treatment promoted CD36 sarcolemmal translocation, where it activated Rac1 and upregulated MMP-9 through Src-Akt/ERK pathway, resulting in redistribution of cortactin, N-WASP and Arp2/3, and finally led to occurrence of finger-like protrusions of actin on cell surface to enhance cell metastasis. Compared with normal-chew diet (NCD) mice, the HFD group exhibited higher level of blood free fatty acid (FFA) and cholesterol (TC), developed larger xenograft LUAD tumors and enhanced tumor cell metastatic potential, which were accompanied by obvious sarcolemmal actin remodeling and were blocked by simultaneous CD36 knockdown in LUAD cells. Consistently, xenografted and tail vein-injected scramble-RNA-A549 cells but not CD36-shRNA-A549 in HFD mice formed metastatic LUAD tumors on the lung. CD36 inhibitor SSO significantly inhibited LUAD cell metastasis to the lung. Collectively, CD36 initiates Src signaling to promote LUAD cell proliferation and actin remodeling-involved metastasis under high-fat environment. Our study provides the new insights that CD36 is a valid target for LUAD therapy.

Targeting CD36 determines nicotine derivative NNK-induced lung adenocarcinoma carcinogenesis.

Smoking carcinogen nicotine-derived nitrosamine ketone (NNK) is the most potent contributor to lung adenocarcinoma (LUAD) development, but the mechanism has not been fully elucidated. Here, we reported that fatty acid translocase CD36 was significantly overexpressed in both human LUAD tissues and NNK-induced A/J mice LUAD tumors. The overexpressed CD36 was positively correlated with Src kinase activation, smoking status, metastasis, and worse overall survival of patients with smoking history. Upon NNK binding with α7 nicotinic acetylcholine receptor (α7nAChR), sarcolemmal CD36 was increased and it interacted with surface α7nAChR and cytosol Src simultaneously, which in turn activated Src and downstream pro-carcinogenic kinase ERK1/2 and Akt, and finally caused LUAD cells to form subcutaneous and pulmonary metastatic tumors. This process could be blocked by CD36 knockdown and CD36 irreversible inhibitor SSO. Furthermore, the effect of NNK was inhibited obviously in CD36-/- A/J mice. Thus, targeting CD36 may provide a breakthrough therapy of LUAD.

Cytotoxic tetronic acid derivatives from the mangrove endophytic fungus Hypomontagnella monticulosa YX702.

Three new tetronic acid derivatives, nodulisporacid A ethyl ester (3), isosporothric acid methyl ester (4), and (R)-3-(methoxycarbonyl)-2-methyleneundecanoic acid (5) were isolated from mangrove endophytic fungus Hypomontagnella monticulosa YX702, together with three known analogues nodulisporacid A (1), nodulisporacid A methyl ester (2), and dihydrosporothriolide (6). The structures of these new compounds were elucidated by analysis of NMR and HR-ESI-MS spectroscopic data. In addition, the absolute configuration of nodulisporacid A (1) was confirmed by single-crystal X-ray diffraction for the first time. Subsequently, the absolute configuration of compounds 2 and 3 were determined by chemical derivatization of nodulisporacid A (1). The absolute configuration of compound 4 and 5 were established by TDDFT ECD calculations. Compounds 1 and 2 exhibited cytotoxic activities against A549 and Hela cancer cell lines with the IC50 values between 5.64 and 8.14 µM.

Overexpression of POLA2 in hepatocellular carcinoma is involved in immune infiltration and predicts a poor prognosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second malignancy worldwide. POLA2 initiates DNA replication, regulates cell cycle and gene repair that promote tumorigenesis and disease progression. However, the prognostic and biological function roles of POLA2 in HCC had not been conclusively determined. METHODS: The expression levels and prognosis role of POLA1 and POLA2 in HCC were analyzed based on TCGA-LIHC database and recruited 24 HCC patients. Gene mutations were analyzed using "maftools" package. POLA2 and immune cells correlations were analyzed by TIMER. POLA2 co-expressed genes functional enrichment were evaluated using Metascape. The mRNA and protein level of POLA2 was detected in HCC cells and tissues. Cell migration, invasion, proliferation, cell cycle and HCC cell lines derived xenograft model were performed to investigate POLA2 biological function. RESULTS: POLA2 was significantly high expressed in HCC than in normal liver tissue in both TCGA-LIHC and our collected HCC samples. In validation cohort, POLA2 significantly related to tumor differentiation, tumor size and Ki-67 (p < 0.05). In TCGA-LIHC cohort, overexpression of POLA2 predicted a low OS and associated with different clinical stages. Multivariate Cox regression showed overexpression of POLA2 effectively distinguished the prognosis at different T, N, M, stages and grades of HCC. POLA2 expression correlated with mutation burden, immune cells infiltration and immune-associated genes expression of HCC. Functional enrichment revealed that POLA2 co-expressed genes were linked to cellular activity, plasma membrane protein complex and leukocyte activity, immune response-regulated cell surface receptor signaling pathway, and immune response-regulated signaling pathway. Moreover, POLA2 was also positively co-expressed with some immune checkpoints (CD274, CTL-4, HAVCR2, PDCD1, PDCD1LG2, TIGIT, and LAG3) (p < 0.001). Gene knockdown revealed that POLA2 promoted proliferation, migration, invasion, and cell cycle of SMMC-7721 and HepG2. The HCC xenograft tumor model also demonstrated remarkably tumor size inhibition, tumor proliferation inhibtion and tumor necrosis promotion when POLA2 knockdown. CONCLUSIONS: POLA2 influenced immune microenvironment and tumor progression of HCC indicated that it might be a potential molecular marker for prognostic evaluation or a therapeutic target for HCC.

Cell recognition based on atomic force microscopy and modified residual neural network.

Cell recognition methods are in high demand in cell biology and medicine, and the method based on atomic force microscopy (AFM) shows a great value in application. The difference in mechanical properties or morphology of cells has been frequently used to detect whether cells are cancerous, but this detection method cannot be a general means for cancer cell detection, and the traditional artificial feature extraction method also has its limitations. In this work, we proposed an analytic method based on the physical properties of cells and deep learning method for recognizing cell types. The residual neural network used for recognition was modified by multi-scale convolutional fusion, attention mechanism and depthwise separable convolution, so as to optimize feature extraction and reduce operation costs. In the method, the collected cells were imaged by AFM, and the processed images were analyzed by the optimized convolutional neural network. The recognition results of two groups of cells (HL-7702 and SMMC-7721, SGC-7901 and GES-1) by this method show that the recognition rate of dataset with the combination of cell surface morphology, adhesion and Young's modulus is higher, and the recognition rate of the dataset with optimal resolution is higher. Our study indicated that the recognition of physical properties of cells using deep learning technology can serve as a universal and effective method for the automated analysis of cell information.

Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation.

Currently, human health due to corona virus disease 2019 (COVID-19) pandemic has been seriously threatened. The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19. However, the efficacy is compromised by the SARS-CoV-2 evolvement and mutation. Here we report the SARS-CoV-2 S protein receptor-binding domain (RBD) inhibitor licorice-saponin A3 (A3) could widely inhibit RBD of SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, XBB and BQ1.1. Furthermore, A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells, with EC50 of 1.016 µM. The mechanism was related with binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis combined with quantum mechanics/molecular mechanics (QM/MM) simulations. Interestingly, phosphoproteomics analysis and multi fluorescent immunohistochemistry (mIHC) respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 MAPK pathways and rebalancing the corresponding immune dysregulation. This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Establishment and validation of nomogram model for the diagnosis of AFP-negative hepatocellular carcinoma.

Introduction: As one of the most common malignant tumors in clinical practice, hepatocellular carcinoma (HCC) is a major threat to human health, where alpha-fetoprotein (AFP) is widely used for early screening and diagnoses. However, the level of AFP would not elevate in about 30-40% of HCC patients, which is clinically referred to as AFP-negative HCC, with small tumors at an early stage and atypical imaging features, making it difficult to distinguish benign from malignant by imaging alone. Methods: A total of 798 patients, with the majority being HBV-positive, were enrolled in the study and were randomized 2:1 to the training and validation groups. Univariate and multivariate binary logistic regression analyses were used to determine the ability of each parameter to predict HCC. A nomogram model was constructed based on the independent predictors. Results: A unordered multicategorical logistic regression analyses showed that the age, TBIL, ALT, ALB, PT, GGT and GPR help identify non-hepatic disease, hepatitis, cirrhosis, and hepatocellular carcinoma. A multivariate logistic regression analyses showed that the gender, age, TBIL, GAR, and GPR were independent predictors for the diagnosis of AFP-negative HCC. And an efficient and reliable nomogram model (AUC=0.837) was constructed based on independent predictors. Discussion: Serum parameters help reveal intrinsic differences between non-hepatic disease, hepatitis, cirrhosis, and HCC. The nomogram based on clinical and serum parameters could be used as a marker for the diagnosis of AFP-negative HCC, providing an objective basis for the early diagnosis and individualized treatment of hepatocellular carcinoma patients.

Correlation between urine vitamin D-binding protein and early-stage renal damage in Type 2 diabetes. / å°¿ç»´ç”Ÿç´ D结合蛋白与2åž‹ç³–å°¿ç— æ‚£è€ æ—©æœŸè‚¾æŸå®³çš„ç›¸å ³æ€§.

OBJECTIVES: The excretion of urinary vitamin D-binding protein (uVDBP) is related to the occurrence and development of early-stage renal damage in patients with Type 2 diabetes (T2DM). This study aims to explore the significance of detecting uVDBP in T2DM patients and its relationship with renal tubules, and to provide a new direction for the early diagnosis of T2DM renal damage. METHODS: A total of 105 patients with T2DM, who met the inclusion criteria, were included as a patient group, and recruited 30 individuals as a normal control group. The general information and blood and urine biochemical indicators of all subjects were collected; the levels of uVDBP, and a marker of tubular injury [urine kidney injury molecule 1 (uKIM-1), urine neutrophil gelatinase-associated lipocalin (uNGAL) and urine retinol-binding protein (uRBP)] were detected by enzyme-linked immunosorbent assay. The results were corrected by urinary creatinine (Cr) to uVDBP/Cr, uKIM-1/Cr, uNGAL/Cr and uRBP/Cr. The Pearson's and Spearman's correlation tests were used to analyze the correlation between uVDBP/Cr and urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR) and markers of tubular injury, and multivariate linear regression and receiver operating characteristic curve were used to analyze the correlation between uVDBP/Cr and UACR or eGFR. RESULTS: Compared with the normal control group, the uVDBP/Cr level in the patient group was increased (P<0.05), and which was positively correlated with UACR (r=0.774, P<0.01), and negatively correlated with eGFR (r=-0.397, P<0.01). There were differences in the levels of uKIM-1/Cr, uNGAL/Cr, and uRBP/Cr between the 2 groups (all P<0.01). The uVDBP/Cr was positively correlated with uKIM-1/Cr (r=0.752, P<0.01), uNGAL/Cr (r=0.644, P<0.01) and uRBP/Cr (r=0.812, P<0.01). The sensitivity was 90.0% and the specificity was 82.9% (UACR>30 mg/g) for evaluation of uVDBP/Cr on T2DM patients with early-stage renal damage, while the sensitivity was 75.0% and the specificity was 72.6% for evaluation of eGFR on T2DM patients with early-stage renal damage. CONCLUSIONS: The uVDBP/Cr can be used as a biomarker in early-stage renal damage in T2DM patients.

Structural Versus Nonstructural Bone Grafting Via the Posterior Approach in the Treatment of Thoracic and Lumbar Tuberculosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Bone grafting is necessary in spinal tuberculosis surgery. Structural bone grafting is considered the gold standard treatment for spinal tuberculosis bone defects; however, nonstructural bone grafting via the posterior approach has recently gained attention. In this meta-analysis, we evaluated the clinical efficacy of structural versus nonstructural bone grafting via the posterior approach in the treatment of thoracic and lumbar tuberculosis. METHODS: Studies comparing the clinical efficacy of structural and nonstructural bone grafting via the posterior approach in spinal tuberculosis surgery were identified from 8 databases from inception to August 2022. Study selection, data extraction, and evaluation of the risk of bias were performed, and meta-analysis was conducted. RESULTS: Ten studies including 528 patients with spinal tuberculosis were enrolled. Meta-analysis revealed no between-group differences in fusion rate (P = 0.29), complications (P = 0.21), postoperative Cobb angle (P = 0.7), visual analog scale score (P = 0.66), erythrocyte sedimentation rate (P = 0.74), or C-reactive protein level (P = 0.14) at the final follow-up. Nonstructural bone grafting was associated with less intraoperative blood loss (P < 0.00001), shorter operation time (P < 0.0001), shorter fusion time (P < 0.01), and shorter hospital stay (P < 0.00001), while structural bone grafting was associated with lower Cobb angle loss (P = 0.002). CONCLUSIONS: Both techniques can achieve a satisfactory bony fusion rate for spinal tuberculosis. Nonstructural bone grafting has the advantages of less operative trauma, shorter fusion time, and shorter hospital stay, making it an attractive option for short-segment spinal tuberculosis. Nevertheless, structural bone grafting is superior for maintaining corrected kyphotic deformities.

Isolated cryptococcal osteomyelitis of the sacrum in an immunocompetent patient: a case report and literature review.

BACKGROUND: Cryptococcus neoformans, an opportunistic fungal pathogen, seldom causes infection in immunocompetent people. Cryptococcal osteomyelitis is an uncommon condition in which Cryptococcus invades the bone. It usually occurs as part of a disseminated infection and rarely in isolation. The spine has been reported as the most common site of cryptococcal osteomyelitis; however, isolated case of sacrum involvement in immunocompetent patients has never been reported. CASE PRESENTATION: We report the case of a 37-year-old man without underlying disease who presented with progressive low back and sacrococcygeal pain. The patient was initially diagnosed with sacral tumour by a local doctor, and subsequently, after admission, was diagnosed with sacral tuberculosis. He was empirically treated with antitubercular drugs. The patient failed to respond to antitubercular drugs and complained of worsening low back pain. Additionally, he developed persistent radiating pain and numbness in his legs. For further diagnosis, we performed a computed tomography-guided puncture biopsy of the sacrum, which revealed granulomatous inflammation with massive macrophage infiltration and special staining revealed a fungal infection. We performed sacral debridement and drainage and obtained purulent specimens for pathological examination and microbial culture. Microbial identification and drug susceptibility tests revealed a Cryptococcus neoformans infection sensitive to fluconazole. Postoperatively, the persistent radiating pain and numbness in the legs resolved. After 12 consecutive weeks of antifungal therapy, all his symptoms resolved. The patient remained without any signs of recurrence at the 8-month follow-up. CONCLUSION: We reported a rare case of isolated sacrum cryptococcal osteomyelitis in an immunocompetent patient. Furthermore, we identified and reviewed 18 published cases of spine cryptococcal osteomyelitis. Immunocompetent individuals are also at risk for cryptococcal osteomyelitis. Clinical manifestation and imaging are insufficient to diagnose cryptococcal osteomyelitis of the spine, and invasive examinations, such as puncture biopsy and fungal examinations, are needed. Antifungal therapy yields satisfactory results for the treatment of cryptococcal osteomyelitis of the spine, however, if the infective lesion is large, especially when it compresses the spinal cord and nerves, a regimen combining aggressive surgery with antifungal therapy is indispensable.

Analysis of phellinus igniarius effects on gastric cancer cells by atomic force microscopy.

Gastric cancer is one of the common malignant tumors in the world, which originates from the gene mutation of human cells. In this work, an atomic force microscope was used to quantitatively detect the changes of multiple physical parameters such as the cell morphology, surface roughness, elasticity modulus and adhesion force before and after Phellinus linteus stimulation. The experimental results show that Phellinus linteus can change the shape of gastric cancer cells (SGC-7901) from flat to spherical, and increase their height and surface roughness values. The adhesion force of cells is reduced and the elasticity modulus is increased. But there are no significant differences in the morphology and mechanical properties of gastric epithelial cells (GES-1). The results indicate that Phellinus linteus has a high anticancer effect on the gastric cancer cells, but has less toxic side effects on the gastric epithelial cells. This work proves that Phellinus linteus can be used as a preferred anticancer drug for the treatment of gastric cancer cells.

Expanding the Scope of Targeted Metabolomics by One-pot Microscale Synthesis and Tailored Metabolite Profiling: Investigation of Bile Acid-Amino Acid Conjugates.

Accurate metabolite characterization plays a vital role in targeted metabolomics. Nonetheless, the library of metabolites is still limited, especially for downstream conjugates, and it is time-consuming to synthesize each of these compounds due to high structural diversity. Herein, a green and smart strategy was developed to expand the scope of targeted metabolomics. The reference standards were synthesized in a one-pot microscale reaction, and the analytical method was tailored using the synthetic products. A group of new metabolites, namely bile acid-amino acid conjugates (BA-AAs), was studied as a proof-of-concept. First, in total 160 BA-AAs were synthesized using a small amount (2 mg each) of bile acids and low-toxic reagents within 4 h. Then, an ultra-high-performance liquid chromatography /Orbitrap-MS method was established to comprehensively profile 202 bile acid derivatives in 20 min. Finally, the method was applied to mice with inflammatory bowel disease (IBD) to discover the accumulation of 70 rare BA-AAs in small intestine and liver, where 55 were first reported from biosamples. These BA-AAs are farnesoid X receptor modulators and might contribute to the development of IBD. Our study demonstrated a feasible approach for the broad-spectrum targeted metabolomics of bile acids.

Histone H3K9 demethylase JMJD2B/KDM4B promotes osteogenic differentiation of bone marrow-derived mesenchymal stem cells by regulating H3K9me2 on RUNX2.

Background: A variety of proteins including epigenetic factors are involved in the differentiation of human bone marrow mesenchymal stem cells. These cells also exhibited an epigenetic plasticity that enabled them to trans-differentiate from adipocytes to osteoblasts (and vice versa) after commitment. Further in-depth study of their epigenetic alterations may make sense. Methods: Chromatin Immunoprecipitation-PCR (ChIP-PCR) was used to detect the methylation enrichment status of H3K9me2 in the Runx2 promoter, alizarin red and alkaline phosphatase (ALP) staining were used to detect osteogenic differentiation and mineralization ability, western blot and quantitative RT-PCR were used to measure the differential expression of osteogenesis-related proteins and genes. Recombinant Lentivirus mediated gain-of-function and loss-of-function study. The scale of epigenetic modification was detected by laser confocal. Results: Our results showed that compared with human bone marrow mesenchymal stem cells (hBMSCs) without osteogenic differentiation treatment, hBMSCs after osteogenic differentiation significantly promoted osteogenic differentiation and mRNA expression such as JMJD2B/KDM4B, osteogenesis-related genes like Runx2 and FAM210A in hBMSCs cells, suggesting that upregulation of JMJD2B/KDM4B is involved in the promoting effect of osteogenesis. After overexpression and silencing expression of JMJD2B, we found a completely opposite and significant difference in mRNA expression of osteogenesis-related genes and staining in hBMSCs. Overexpression of JMJD2B/KDM4B significantly promoted osteogenic differentiation, suggesting that JMJD2B/KDM4B could promote osteogenesis. In addition, ChIP-PCR showed that overexpression of JMJD2B/KDM4B significantly reversed the methylation enrichment status of H3K9me2 in Runx2 promoter. Furthermore, overexpression of JMJD2B/KDM4B significantly reverses the inhibitory effect of BIX01294 on H3K9me2, suggesting that JMJD2B/KDM4B regulates the osteogenic differentiation of hBMSCs by changing the methylation status of H3K9me2 at the Runx2 promoter. Conclusions: Taken together, these results suggest that JMJD2B/ KDM4B may induce the osteogenic differentiation of hBMSCs by regulating the methylation level of H3K9me2 at the Runx2 promoter.

Simultaneous methanogenesis and denitrification coupled with nitrifying biofilm for high-strength wastewater treatment: Performance and microbial mechanisms.

A combined system consisting of an upflow blanket filter (UBF) and a moving-bed biofilm reactor (MBBR) was developed for the simultaneous removal of organic matters and ammonia from high-strength wastewater. With a constant COD of approximately 2000 mg/L and ammonium nitrogen in a series of concentrations (e.g., 50, 200 and 400 mg/L in stages I to III) of the influent wastewater, the removal efficiencies of COD, ammonium nitrogen and total nitrogen reached 96.10%-98.19%, 100%, and 79.12%-82.15%, respectively. With the increase of influent ammonia nitrogen concentration, the specific methanogenic activity of the UBF granules decreased significantly, while the specific denitrification rates of the UBF granules and specific nitrification rates of the MBBR biofilms increased significantly. Microbial community analysis showed that Methanobacterium and Methanosaeta were the dominant methanogens in the UBF granules, while Candidatus Competibacter, Thauera and Acinetobacter were identified as dominant denitrifiers. In addition, nitrifiers were enriched in MBBR biofilms at 11.33% and 13.87% of the average abundance of Nitrosomonas and Nitrospira, respectively, at stage III (influent ammonium at 400 mg/L, COD/NH4+-N =  5). The ecological network analysis, including full-networks and sub-networks, indicated that the interactions between methanogens and denitrifiers in the UBF granules were strong when the influent ammonium concentration reached 400 mg/L. No intensive interactions were observed among the functional bacteria in the MBBR biofilms over the entire operation. Overall, this study provides a new strategy for the application and construction of efficient biological processes to achieve simultaneous removal of organic matter and nitrogen for high-strength wastewater treatment.

Methodology of network pharmacology for research on Chinese herbal medicine against COVID-19: A review.

Traditional Chinese medicine, as a complementary and alternative medicine, has been practiced for thousands of years in China and possesses remarkable clinical efficacy. Thus, systematic analysis and examination of the mechanistic links between Chinese herbal medicine (CHM) and the complex human body can benefit contemporary understandings by carrying out qualitative and quantitative analysis. With increasing attention, the approach of network pharmacology has begun to unveil the mystery of CHM by constructing the heterogeneous network relationship of "herb-compound-target-pathway," which corresponds to the holistic mechanisms of CHM. By integrating computational techniques into network pharmacology, the efficiency and accuracy of active compound screening and target fishing have been improved at an unprecedented pace. This review dissects the core innovations to the network pharmacology approach that were developed in the years since 2015 and highlights how this tool has been applied to understanding the coronavirus disease 2019 and refining the clinical use of CHM to combat it.